A 20-year-old female with difficulties in running and climbing stairs since age 10 and suspected of having spinal muscular atrophy (SMA) type III (Kugelberg-Welander disease) was diagnosed with GM2 gangliosidosis at the Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, and Sapir Medical Center, Kfar-Sava, Israel. Amyotrophy extended to the middle of the thighs in the lower limbs and had a distal glove distribution in the upper limbs. Deep tendon reflexes were present except for the ankle jerks. The survival motor neuron (SMN) gene, lacking in SMA, showed no deletion. Biochemical studies showed increased accumulation of GM2 ganglioside and deficiency of hexosaminidase A (Hex A) activity in fibroblasts. In the HEXA gene, two mutations occurred, and the patient was a compound heterozygote, with each allele containing a different mutation. [1]

COMMENT. Progressive spinal muscular atrophy (SMA) type III (Kugelberg-Welander disease) and GM2 gangliosidosis are both autosomal recessive in inheritance. Molecular studies on a proband thought to have SMA have uncovered a GM2 gangliosidosis as the cause of the progressive amyotrophy. The SMA gene showed no deletion while the HEXA gene had two mutations. At the onset of GM2 gangliosidosis, clinical manifestations are variable and the differential diagnosis may include SMA or Friedreich ataxia.